Method for producing 4-amino-5-chloro-1-phenyl pyridazinone-(6)

ABSTRACT

In a process for preparing 4-amino-5-chloro-1-phenylpyridazin-6-one by reacting 4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia in the presence of a catalyst, the catalyst used is soluble in the aqueous alkaline reaction medium but is essentially insoluble in the reaction medium which has been acidified after removal of the 4-amino-5-chloro-1-phenylpyridazin-6-one. 
     The process of the present invention makes it possible for the catalyst to be recovered and reused in a simple manner.

The present invention relates to a process for preparing4-amino-5-chloro-1-phenylpyridazin-6-one by reacting4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia in thepresence of a catalyst.

4-Amino-5-chloro-1-phenylpyridazin-6-one (chloridazon) is used as aherbicide for selective control of weeds in sugar beet. This compound isprepared as described in GB 871674 by reacting4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia under pressureand at elevated temperature. This gives an isomer mixture of about 80%by weight of 4-amino-5-chloro-1-phenylpyridazin-6-one and about 20% byweight of 5-amino-4-chloro-1-phenylpyridazin-6-one. The isolation of thechloridazon from this isomer mixture by extraction of the undesiredisomer with nonpolymer solvents is described, for example, in DE 16 20186.

Furthermore, attempts have been made to carry out the reaction in such away that a purer product is obtained. Thus, DD 131172 describes theabove reaction in organic solvents, which gives a purer product.However, the use of organic solvents in place of water is a drawback. EP26 847 A and EP 28 359 A describe the reaction of4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia under pressurein the presence of phenolic compounds having substituents which makethese compounds soluble in the aqueous reaction medium. Examples of suchcompounds are 4-phenolsulfonic acid, 3-hydroxypyridone and3-hydroxypyridine. very good yields of chloridazon of high purity areobtained in this way. The catalysts used cannot be reused in the form ofthe solution in the reaction medium because this would involverecirculation of the ammonium chloride formed in the reaction. On theother hand, recovery of the catalysts from the aqueous reaction mediumis possible to only a very limited extent, even by extraction withorganic solvents, because of their high solubility in water.

It is an object of the present invention to provide a process forpreparing chloridazon in which the chloridazon is obtained in high yieldand high purity and the catalyst employed can be reused in a simplemanner.

We have found that this object is achieved by a process in which4,5-dichloro-1-phenylpyridazin-6-one is reacted with aqueous ammonia inthe presence of a catalyst which is soluble in the reaction medium usedbut is essentially insoluble in the reaction medium at an acid pH.

The present invention accordingly provides a process for preparing4-amino-5-chloro-1-phenylpyridazin-6-one by reacting4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia in thepresence of a catalyst which is soluble in the aqueous reaction mediumused (i.e. at an alkaline pH) but is essentially insoluble in thereaction medium which has been acidified after removal of theprecipitated 4-amino-5-chloro-1-phenylpyridazin-6-one.

The ammonia is used in a large excess for the reaction. The pH of theaqueous reaction medium is thus in the alkaline range. The catalystsused here are soluble in this reaction medium.

If desired, the excess ammonia is removed after the reaction, e.g. bystripping before or during cooling of the reaction mixture.

The chloridazon obtained precipitates as a solid after the reaction,particularly on cooling the reaction mixture. It is isolated from thereaction medium in a customary manner, for example by filtration. Thereaction medium remaining after isolation of the chloridazon (motherliquor) has an alkaline pH. Setting of an acid pH, for example pH<6, inparticular <4 and particularly preferably <2, by means of an inorganicacid such as hydrochloric acid, sulfuric acid or phosphoric acid or anorganic acid such as formic acid or acetic acid makes the catalystinsoluble in the reaction medium. In general, it precipitates as anamorphous or crystalline solid and can thus be isolated in a simplemanner, for example by filtration. For the purposes of the presentinvention, “insoluble in the reaction medium” means that the catalysthas a solubility in the reaction medium of not more than 5 g/l, inparticular not more than 2 g/l.

Suitable catalysts are, in particular, phenolic compounds whose aromaticring system is substituted not only by the phenolic hydroxy group butalso by at least one further electron-withdrawing substituent withoutacidic hydrogen atoms. For the purposes of the present invention,phenolic compounds are compounds having an aromatic carbocyclic orheterocyclic ring system (in particular phenyl, naphthyl, pyridyl,pyrimidyl, etc.) which bears at least one hydroxy group.

The aromatic ring system generally bears one or two electron-withdrawingsubstituents. These are, in particular, SO₂R¹, NO₂, COR¹, CF₃, CN andOR¹, where R¹ is C₁-C₆-alkyl or phenyl which may be substituted by 1 or2 hydroxy groups.

Phenolic compounds which can be used are, for example, 2-, 3- or4-nitrophenol, 2,4-dinitrophenol, 4-benzoylphenol,4,4′-dihydroxybenzophenone and, in particular,bis(hydroxyphenyl)sulfones such as bis(4-hydroxyphenyl)sulfone.

The salts of the phenolic compounds, e.g. the alkali metal or alkalineearth metal salts and the ammonium salts, are also suitable.

The phenolic compounds are water-soluble in the phenoxide form but areessentially water-insoluble in the form of the free phenols. They cantherefore be recovered essentially quantitatively, but at least to anextent of 80%, in particular at least 90%, and be used for furtherreactions. In this way, they are also separated from the ammoniumchloride formed in the reaction. Addition of bases such as aqueoussodium hydroxide to the reaction medium obtained after recovery of thecatalyst enables the ammonia bound in the form of ammonium chloride tobe liberated again and recovered.

The reaction of 4,5-dichloro-1-phenylpyridazin-6-one with ammonia can becarried out in one or two stages. In the single-stage variant, thereactants and the catalyst are introduced simultaneously. In thetwo-stage variant, a solution of the catalyst, for example a solution ofa sodium or ammonium salt of the catalyst, is first reacted with4,5-dichloro-1-phenylpyridazin-6-one so as to replace the chlorine atomin the 4 position by the corresponding phenoxide to give thecorresponding intermediate. For example, whenbis(4-hydroxyphenyl)sulfone is used as catalyst,4-(4-hydroxyphenylsulfonyl)phenyloxy-5-chloro-1-phenylpyridazin-6-one isobtained as intermediate. The respective intermediate is subsequentlyreacted with aqueous ammonia under pressure to convert it into thedesired chloridazon product.

The process of the present invention is generally carried out in thetemperature range from 80 to 200° C., in particular from 100 to 150° C.and preferably from 100 to 140° C.

The amount of catalyst employed can be varied within a wide range. Thereaction is advantageously carried out in the presence of from 1 to 200mol %, in particular from 20 to 150 mol %, of catalyst, based on4,5-dichloro-1-phenylpyridazin-6-one.

The process is carried out at a pressure which is generally in the rangefrom 1 to 50 bar, preferably from 3 to 20 bar. The process isparticularly preferably carried out at the pressure established in theclosed reaction vessel at the reaction temperature selected. However, itis also possible to increase the pressure in the closed vessel duringthe reaction by injection of ammonia. In this case, part of the injectedammonia dissolves in the aqueous reaction medium.

The following examples illustrate the invention without limiting it inany way.

EXAMPLE 1 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one(chloridazon) using bis(4-hydroxyphenyl)sulfone

In a 250 ml stirring autoclave, 100 parts of water, 70 parts (1.03 mol)of 25% strength ammonia, 12 parts (0.05 mol) of4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) and 12.5 parts(0.05 mol) of bis(4-hydroxyphenyl)sulfone were stirred at 130° C. for 8hours. The pressure rose steadily to about 5 bar. After stirringovernight, the autoclave was depressurized to atmospheric pressure, withthe excess ammonia being stripped off. After cooling to roomtemperature, the precipitated solid was filtered off, washed with waterand dried at 50° C. in a vacuum drying oven.

This gave 10.1 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one havinga purity of 98.8%; this corresponds to a yield of 90% of theory. The pHof the filtrate was adjusted to 1.5 using 60% strength sulfuric acid andthe precipitated bis(4-hydroxyphenyl)sulfone was filtered off, washedwith water and dried. This gave 12.6 parts ofbis(4-hydroxyphenyl)sulfone having a purity of 99.2%; this correspondsto 100% of the amount of catalyst used.

EXAMPLE 2 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one(chloridazon) using bis(4-hydroxyphenyl) sulfone as catalyst

In a 1 l stirring autoclave, 300 parts of water, 210 parts (3.09 mol) of25% strength ammonia, 36 parts (0.15 mol) of4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) and 37.5 parts(0.15 mol) of bis(4-hydroxyphenyl)sulfone were stirred at 130° C. for 8hours. The pressure rose steadily to about 5 bar. After stirringovernight, the autoclave was depressurized to atmospheric pressure, withthe excess ammonia being stripped off. After cooling to roomtemperature, the precipitated solid was filtered off, washed with waterand dried at 50° C. in a vacuum drying oven.

This gave 30.7 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one havinga purity of 99.9%; this corresponds to a yield of 92.3% of theory. ThepH of the filtrate was adjusted to 1.4 using 60% strength sulfuric acidand the precipitated bis(4-hydroxyphenyl)sulfone was filtered off andwashed with water. This gave 53.5 parts of bis(4-hydroxyphenyl)sulfonehaving a water content of 30%. This corresponds to 99.8% of the amountof catalyst used.

EXAMPLE 3 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one usingrecycled bis(4-hydroxyphenyl)sulfone

The moist catalyst from Example 2 was stirred at 130° C. with 300 partsof water, 210 parts (3.09 mol) of 25% strength ammonia and 36 parts(0.15 mol) of 4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) for 8hours in the 1 l stirring autoclave. A pressure of 6 bar wasestablished. After stirring overnight, the autoclave was depressurizedto atmospheric pressure, with the excess ammonia being stripped off.After cooling to room temperature, the precipitated solid was filteredoff, washed with water and dried at 50° C. in a vacuum drying oven.

This gave 30.5 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one havinga purity of 99.5%; this corresponds to a yield of 91.3% of theory. ThepH of the filtrate was adjusted to 1.4 using 60% strength sulfuric acidand the precipitated bis(4-hydroxyphenyl)sulfone was filtered off,washed with water and dried. This gave 37.1 parts ofbis(4-hydroxyphenyl)sulfone having a purity of 99.5%; this correspondsto 98.4% of the amount of catalyst used.

EXAMPLE 4 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one(chloridazon) using 4-nitrophenol as catalyst

In a 250 ml stirring autoclave, 100 parts of water, 70 parts (1.03 mol)of 25% strength ammonia, 12 parts (0.05 mol) of4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) and 14.2 parts (0.1mol) of 98%-pure 4-nitrophenol were stirred at 130° C. for 8 hours. Thepressure rose to about 4 bar. After stirring overnight, the autoclavewas depressurized to atmospheric pressure, with the excess ammonia beingstripped off. After cooling to room temperature, the precipitated solidwas filtered off, washed with water and dried at 50° C. in a vacuumdrying oven.

This gave 10.3 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one havinga purity of 99.1%; this corresponds to a yield of 92.2% of theory. ThepH of the filtrate was adjusted to 1.0 using 60% strength sulfuric acidand the precipitated 4-nitrophenol was filtered off, washed with waterand dried. This gave 14 parts of 4-nitrophenol having a purity of 98.1%;this corresponds to 98.8% of the amount of catalyst used.

EXAMPLE 5 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one(chloridazon) using 4,4′-dihydroxybenzophenone as catalyst

In a 250 ml stirring autoclave, 100 parts of water, 70 parts (1.03 mol)of 25% strength ammonia, 12 parts (0.05 mol) of4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) and 10.7 parts(0.05 mol) of 4,4′-dihydroxybenzophenone were stirred at 130° C. for 8hours. The pressure rose steadily to about 4.5 bar. After stirringovernight, the autoclave was depressurized to atmospheric pressure, withthe excess ammonia being stripped off. After cooling to roomtemperature, the precipitated solid was filtered off, washed with waterand dried at 50° C. in a vacuum drying oven.

This gave 10.2 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one havinga purity of 98.9%; this corresponds to a yield of 91.1% of theory. ThepH of the filtrate was adjusted to 1.5 using 60% strength sulfuric acidand the precipitated 4,4′-dihydroxybenzophenone was filtered off, washedwith water and dried. This gave 10.9 parts of 4,4′-dihydroxybenzophenonehaving a purity of 98.3%; this corresponds to 100% of the amount ofcatalyst used.

EXAMPLE 6 Preparation of 4-amino-5-chloro-1-phenylpyridazin-6-one(chloridazon) using recycled 4,4′-dihydroxybenzophenone as catalyst

The catalyst from Example 5 was stirred at 130° C. with 100 parts ofwater, 70 parts (1.03 mol) of 25% strength ammonia and 12 parts (0.05mol) of 4,5-dichloro-1-phenylpyridazin-6-one (purity: 99.7%) for 8 hoursin a 250 ml stirring autoclave. A pressure of 4.3 bar was established.After stirring overnight, the autoclave was depressurized to atmosphericpressure, with the excess ammonia being stripped off. After cooling toroom temperature, the precipitated solid was filtered off, washed withwater and dried at 50° C. in a vacuum drying oven.

This gave 10 parts of 4-amino-5-chloro-1-phenylpyridazin-6-one having apurity of 99.1%; this corresponds to a yield of 89.5% of theory. The pHof the filtrate was adjusted to 1.5 using 60% strength sulfuric acid andthe precipitated 4,4′-dihydroxybenzophenone was filtered off, washedwith water and dried. This gave 10.7 parts of 4,4′-dihydroxybenzophenonehaving a purity of 99.2%; this corresponds to 99.2% of the amount ofcatalyst used.

We claim:
 1. A process for preparing4-amino-5-chloro-1-phenyl-pyridazin-6-one comprising a) reacting4,5-dichloro-1-phenylpyridazin-6-one with aqueous ammonia in thepresence of a catalyst which is soluble in the aqueous alkaline reactionmedium but becomes essentially insoluble in the reaction medium whenthis is being acidified, b) removing the precipitated4-amino-5-chloro-1-phenyl-pyridazin-6-one, c) acidifying the reactionmedium, and d) isolating the precipitated catalyst, wherein the catalystused is a carbocyclic phenolic compound or a salt thereof, whosearomatic ring system is substituted not only by the phenolic hydroxygroup or groups but also by at least one further electron-withdrawingsubstituent without acidic hydrogen atoms, selected from SO₂R¹, NO₂,COR¹, CF₃ or CN, where R¹ is C₁-C₆-alkyl or phenyl which may besubstituted by 1 or 2 hydroxy groups.
 2. A process as claimed in claim1, wherein the catalyst used is bis(4-hydroxyphenyl)sulfone, 2-, 3- or4-nitrophenol or 2,4-dinitrophenol.
 3. A process as claimed in claim 1,wherein the catalyst is used in an amount of from 1 to 200 mol %, basedon 4,5-dichloro-1-phenylpyridazin-6-one.
 4. A process as claimed inclaim 1, wherein the reaction is carried out at a temperature in therange from 80 to 200° C.
 5. A process as claimed in claim 1, wherein thereaction is carried out at a pressure in the range from 1 to 50 bar.